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Abstract Purpose The present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD). Patients and methods We retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20–50 years) and an old COPD group (aged > 50 years). Results A total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%). Conclusion Young COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients.

The bacterium Klebsiella pneumoniae (Kp) was the primary pathogen of hospital-acquired infection, but the current detection method could not rapidly and conveniently identify Kp. Recombinase polymerase amplification (RPA) was a fast and convenient isothermal amplification technology, and the clustered regularly interspaced short palindromic repeats (CRISPR) system could rapidly amplify the signal of RPA and improve its limit of detection (LOD). In this study, we designed three pairs of RPA primers for the rcsA gene of Kp, amplified the RPA signal through single-strand DNA reporter cleavage by CRISPR/Cas12a, and finally analyzed the cleavage signal using fluorescence detection (FD) and lateral flow test strips (LFTS). Our results indicated that the RPA-CRISPR/Cas12a platform could specifically identify Kp from eleven common clinical pathogens. The LOD of FD and LFTS were 1 fg/μL and 10 fg/μL, respectively. In clinical sample testing, the RPA-CRISPR/Cas12a platform was consistent with the culture method and qPCR method, and its sensitivity and specificity were 100% (16/16) and 100% (9/9), respectively. With the advantages of detection speed, simplicity, and accuracy, the RPA-CRISPR/Cas12a platform was expected to be a convenient tool for the early clinical detection of Kp.

ObjectiveThe study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism.MethodsThe nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial–choroid–sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR.ResultsThe current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone.ConclusionCombining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.

Background The prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20–35 years are not well understood, despite its potential implications for the development of chronic pulmonary disease and overall prognosis.Methods A retrospective cohort study was conducted among young adults aged 20–35 years old, using data from the National Health and Nutrition Examination Survey, National Death Index and Centers for Medicare & Medicaid Services. Participants were categorised into a low FEV1 group (pre-bronchodilator FEV1%pred

Abstract Background In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. Methods We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). Results A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P

Abstract Background Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders. Objective To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders. Methods Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on “the role of NES on retinal diseases” published up until September 2023. Possible biases were identified with the adopted SYRCLE’s tool. Results Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE’s risk of bias tool. Conclusion This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.

Abstract Background Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP. Methods Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF). Discussion The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial. Trial registration Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635 . Registered on 5 January 2023

Introduction:Salmonella was one of the most common bacteria that caused foodborne illness, with S. typhimurium (Salmonella typhimurium) and S. enteritidis (Salmonella enteritidis) infections accounting for more than 75% of human salmonella infections.Methods: In this study, we developed a method of dual recombinase polymerase amplification (RPA) combined with a lateral flow dipstick for the rapid detection of S. typhimurium and S. enteritidis in clinical specimens (stool).Results: The entire reaction process, including amplification and result reading, could be completed within 65 min. The detection limits of S. typhimurium and S. enteritidis in pure culture samples were 5.23 × 101 CFU/mL and 3.59 × 101 CFU/mL, respectively. The detection limits of S. typhimurium and S. enteritidis in artificially contaminated samples were 8.30 × 101 CFU/mL and 2.70 × 102 CFU/mL, respectively. In addition, the method had no cross-reaction with other pathogenic microorganisms. The results in clinical samples were fully consistent with those obtained using Bacterial Analysis Manual, with sensitivity and specificity were 100% (8/8) and 100% (17/17) for S. typhimurium and 100% (4/4) and 100% (21/21) for S. enteritidis, respectively.Discussion: The detection limits of S. typhimurium and S. enteritidis in artificially contaminated samples were higher than those in pure culture samples, which might be attributed to the inherent complex composition of artificially contaminated samples. In addition, the detection limits of S. typhimurium and S. enteritidis in the same sample were also different, which might be attributed to different amplification efficiency of two target genes in the same reaction system.Conclusion: This assay had potential application outdoors, as it could be performed within 1 h at 38°C without a complex instrument, and the results could be observed with the naked eye. In conclusion, the dual RPA-LFD assay established in this study had practical significance for the rapid detection of S. typhimurium and S. enteritidis in the future.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) poses a severe nosocomial threat, prompting a need for efficient detection methods. Traditional approaches, such as bacterial culture and PCR, are time-consuming and cumbersome. The CRISPR-based gene editing system offered a potential approach for point-of-care testing of CRAB.MethodsWe integrated recombinase polymerase amplification (RPA) and CRISPR-Cas12a system to swiftly diagnose CRAB-associated genes, OXA-51 and OXA-23. This multiplex RPA-CRISPR-Cas12a system eliminates bulky instruments, ensuring a simplified UV lamp-based outcome interpretation.ResultsOperating at 37°C to 40°C, the entire process achieves CRAB diagnosis within 90 minutes. Detection limits for OXA-51 and OXA-23 genes are 1.3 × 10−6 ng/μL, exhibiting exclusive CRAB detection without cross-reactivity to common pathogens. Notably, the platform shows 100% concordance with PCR when testing 30 clinical Acinetobacter baumannii strains.ConclusionIn conclusion, our multiplex RPA coupled with the CRISPR-Cas12a system provides a fast and sensitive CRAB detection method, overcoming limitations of traditional approaches and holding promise for efficient point-of-care testing.

The coordination and balance between agricultural development (AD) and agricultural carbon emissions (ACE) is one of the most important ways to boost the high-quality development of agriculture in the Beijing-Tianjin-Hebei region. Taking 13 prefecture-level cities in the Beijing-Tianjin-Hebei region as the research object, this study uses the comprehensive evaluation method and Tapio decoupling model to analyze the decoupling effect between the AD level and the Agricultural Carbon emissions intensity (ACEI) from 2000 to 2020, based on the assessment of AD status and the calculation of Agricultural Carbon emissions quantities (ACEQ) and ACEI. It found that: (1) From 2000 to 2020, the AD in the Beijing-Tianjin-Hebei region generally showcased a gradual increase trend, and demonstrated a basic feature that AD in the northern areas was higher than that in the southern ones. (2) From 2000 to 2020, the ACEQ in the Beijing-Tianjin-Hebei region showed a trend of first increasing and then decreasing, with a spatial distribution feature that the ACEQ in the southern cities was higher than that in the northern ones. Regarding the source of ACE, the livestock and poultry farming took the highest proportion. ACEI was decreasing year by year, higher in the southern areas than in the northern ones. (3) The main types of decoupling in the Beijing-Tianjin-Hebei region were strong decoupling, recession decoupling, strong negative decoupling, weak negative decoupling, recession coupling, and expansion negative coupling. The decoupling relationship between AD and ACEI were in dynamic change, but the change trend of the decoupling relationship was optimistic. The results of this study deliver certain deployable practice value for improving the sustainability of regional agricultural green development and ecological environmental protection.

Controlled-release urea (CRU) fertilizers are widely used in agricultural production to reduce conventional nitrogen (N) fertilization-induced agricultural greenhouse gas emissions (GHGs) and improve N use efficiency (NUE). However, the long-term effects of different CRU fertilizers on GHGs and crop yields in vegetable fields remain relatively unexplored. This study investigated the variations in GHG emissions at four growth stages of lettuce in the spring and autumn seasons based on a five-year field experiment in the North China Plain. Four treatments were setup: CK (without N application), U (conventional urea—N application), ON (20% reduction in urea—N application), CRU (20% reduction in polyurethane-coated urea without topdressing), and DCRU (20% reduction in polyurethane-coated urea containing dicyandiamide [DCD] without topdressing). The results show that N application treatments significantly increased the GHG emissions and the lettuce yield and net yield, and DCRU exhibited the lowest N2O and CO2 emissions, the highest lettuce yield and net yield, and the highest lettuce N content of the N application treatments. When compared to U, the N2O emission peak under CRU and DCRU treatments was notably decreased and delayed, and their average N2O emission fluxes were significantly reduced by 10.20–20.72% and 17.51–29.35%, respectively, leading to a significant reduction in mean cumulative N2O emissions during the 2017–2021 period. When compared to U, the CO2 fluxes of DCRU significantly decreased by 8.0–16.54% in the seedling period, and mean cumulative CO2 emission decreased by 9.28%. Moreover, compared to U, the global warming potential (GWP) and greenhouse gas intensity (GHGI) of the DCRU treatment was significantly alleviated by 9.02–17.13% and 16.68–20.36%, respectively. Compared to U, the N content of lettuce under DCRU was significantly increased by 6.48–17.25%, and the lettuce net yield was also significantly increased by 5.41–7.71%. These observations indicated that the simple and efficient N management strategy to strike a balance between enhancing lettuce yields and reduce GHG emissions in open-field lettuce fields could be obtained by applying controlled-release urea containing DCD without topdressing.

Striga asiatica (L.) Kuntze 1891 is a hemiparasitic plant native to Asia and Africa. It is invasive and causes yield losses in crops such as corn, rice and sorghum. Lack of chloroplast genomic data has limited research into its obligate parasitic lifestyle. In this study, the complete chloroplast genome of Striga asiatica was sequenced and characterized. It is a quadripartite structure with a total length of 191,085 bp and a GC content of 37.86%. It has a large single copy region (LSC) of 51,406 bp, a small single copy region (SSC) of 273 bp, and two copies of the reverse repeat sequence (IRA and IRB) of 69,703 bp. A total of 122 protein-coding genes, 8 rRNA genes, and 44 tRNA genes were annotated in the chloroplast genome. There were a lot of ndh gene deletions and pseudogenizations in this chloroplast genome. For example, ndhA, D, E, H, I, and K were all pseudogenes because they were missing the 5′ end start codon. ndhB, C, and J had shorter gene lengths than their homologs, and ndhF and ndhG were missing genes. The phylogenetic tree reveals that all Striga species form a clade, and a bootstrap value of 100 indicates that S. asiatica is closely related to Striga hermonthica and Striga sepera. The comprehensive chloroplast genomic resource of S. asiatica would assist researchers in comprehending hemiparasitic mechanisms, molecular markers, and evolutionary patterns of the genus Striga.

To reduce crop-related water consumption and enhance agricultural water resource efficiency in the Beijing–Tianjin–Hebei region, this study employed the AquaCrop model to simulate crop yield and irrigation water requirements and calculated the water scarcity footprint (WSF). The results were as follows: (1) The AquaCrop model exhibited strong applicability, with R2, RMSE (Root Mean Square Error), EF (Nash–Sutcliffe model efficiency coefficient) and d values of 0.9611, 6.6%, 0.91, and 0.98 (winter wheat), and 0.9571, 5.5%, 0.95, and 0.99 (summer maize) for canopy cover simulation. Similarly, aboveground biomass simulation yielded values of 0.9661, 0.8 t/ha, 0.93, and 0.98 (winter wheat), and 0.9087, 1.3 t/ha, 0.90, and 0.98 (summer maize). Winter wheat soil moisture content simulation showed an R2 of 0.9706, RMSE of 3.7 mm, EF of 0.93, and d of 0.98. (2) The AquaCrop model simulated the winter wheat and summer maize yields and irrigation water requirements for the years 2009, 2014, and 2019, validating the scalability and spatial visualization capabilities of GeoSim in extending AquaCrop simulations. (3) Integrating the water footprint and the water resources system, this study assessed the WSFs of winter wheat and summer maize. From 2009 to 2019, winter wheat production in the region increased by 25.08%, and summer maize production increased by 37.39%. The WSF of winter wheat decreased, whereas the WSF of summer maize increased. It is recommended to reduce crop cultivation areas in regions such as Daming County, Ningjin County, and Dingzhou City while further improving irrigation water efficiency, which would facilitate the sustainable utilization of water resources in the area.

Agricultural green development (AGD) plays an important role in achieving a sustainable society. This paper evaluates the AGD level of Beijing from 1978 to 2022 by means of a comprehensive evaluation method, coupling coordination degree (CCD), and grey relational degree model (GRA) with the purpose of exploring relevant stages and characteristics, as well as analyzing the characteristics of different stages and the coupling relationship of various factors and quantitatively calculating the driving factors for AGD change. The results showed that: 1) the AGD level of Beijing generally improved from 1978 to 2022, mainly involving four stages of steady rising, fluctuating, oscillating decreasing, and rapid upgrading; 2) the CCD of the development subsystems of AGD, agricultural resource utilization, agricultural environment conditions, agricultural industry development, and farmers’ living standard, all rose and the coordination type of each subsystem gradually went through a verge imbalance stage, reluctantly coordinated stage, and primary coordinated stage to an intermediate coordinated stage, and then reached a well-coordinated stage in 2019; 3) the AGD level of Beijing is influenced by economic development, the industrial structure, urbanization, technological progress, and agricultural structure. Finally, some policy suggestions to promote AGD in Beijing are put forward. This paper is of great significance to promoting the green and sustainable development of agriculture in Beijing and provides technical support and policy guidance for AGD in other regions.

Retinitis pigmentosa (RP) is the most common genetic disorder that causes blindness. At present, there exists no remedy for the disease. The aim of the current research was to investigate the protective effect of Zhangyanming Tablets (ZYMT) in a mouse model of RP, and explore the underlying mechanism. Eighty RP mice were randomly divided into two groups. The mice in ZYMT group were administered with ZYMT suspension(0.0378 g/mL), while the mice in model group were given the same volume of distilled water. At day 7 and day 14 after intervention, electroretinogram (ERG), fundus photography, and histological examination were used to assess the retinal function and structure. TUNEL, immunofluorescence and qPCR were used to evaluate cell apoptosis and expressions of Sirt1, Iba1, Bcl-2, Bax and Caspase-3. A significantly shortened latency of ERG waves was observed in ZYMT-treated mice, in comparison to those in the model group (P

Objective To investigate the effect of mesenchymal stem cells (MSCs) on TYK2 phosphorylation in psoriasis-like dermatitis induced by imiquimod cream in mice. Methods The mouse model of psoriasis-like dermatitis was induced by imiquimod cream (IMQ). The mice were randomly divided into blank group, IMQ group and IMQ+MSC group. The changes in skin lesion severity, epidermal thickness, inflammatory cell infiltration and TYK2 phosphorylation level were compared among the groups by HE staining, immunofluorescence and Western blotting. Results Compared with the blank group, the mice in IMQ group showed erythema, scales and increased PASI score. HE staining showed parakeratosis, Munro′s microabscesses and acanthosis. Immunofluorescence showed infiltration of a large number of CD4+T cells and dendritic cells in the dermis. In comparison to IMQ alone, treatment with MSCs lowered the severities of both erythema and scales, and decreased PASI score and dermal infiltration of CD4+T cells and dendritic cells. In addition, the levels of TYK2 phosphorylation in IMQ group were significantly higher than that in blank group (1.233±0.163 vs 0.634±0.117, P

After the outbreak of SARS-CoV-2, nucleic acid testing quickly entered people’s lives. In addition to the polymerase chain reaction (PCR) which was commonly used in nucleic acid testing, isothermal amplification methods were also important nucleic acid testing methods. Among several common isothermal amplification methods like displaced amplification, rolling circle amplification, and so on, recombinase polymerase amplification (RPA) was recently paid more attention to. It had the advantages like a simple operation, fast amplification speed, and reaction at 37-42°C, et al. So it was very suitable for field detection. However, there were still some disadvantages to RPA. Herein, our review mainly summarized the principle, advantages, and disadvantages of RPA. The specific applications of RPA in bacterial detection, fungi detection, virus detection, parasite detection, drug resistance gene detection, genetically modified food detection, and SARS-CoV-2 detection were also described. It was hoped that the latest research progress on RPA could be better delivered to the readers who were interested in RPA.

Abstract Background To explore the effect of applying a comprehensive unit-based safety program (CUSP) in the intrahospital transfer of patients with critical diseases. Methods A total of 426 critically ill patients in the first affiliated Hospital of Anhui Medical University from August 2018 to February 2019 were divided into two groups according to the time of admission. Overall, 202 patients in the control group were treated with the routine transfer method, and 224 patients in the observational group were treated with the transfer method based on the CUSP model. The safety culture assessment data of medical staff, the occurrence rate of adverse events and related causes, the time of transfer, and the satisfaction of patients’ relatives to the transfer process were compared before and after implementation of the transfer model between the two groups. Results Before and after the implementation of the CUSP mode transfer program, there were significant differences in the scores of all dimensions of the safety culture assessment of medical staff (P

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR2000035990 . Registered on 21 August 2020.

What is the interplay of high-tech industrial agglomeration and urban innovation? How does high-tech industrial agglomeration affect urban innovation? What are the heterogeneous effects of high-tech industry agglomeration on urban innovation in different conditions? To answer these questions, this paper analyzes the interrelationship between high-tech industry agglomeration and urban innovation based on panel data of China’s Yangtze River Delta urban agglomeration from 2010 to 2019. We discuss the influence mechanism of high-tech industrial agglomeration on urban innovation by exploring the mediating effect of industrial structure optimization and the threshold effect of industrial attributes. The heterogeneous impact of high-tech industry agglomeration on urban innovation is also been further studied. We find that (1) the interaction relationship between high-tech industry agglomeration and urban innovation output is positive. (2) The advancement of industrial structure plays a positive intermediary role between high-tech industrial agglomeration and urban innovation output, while the rationalization of industrial structure shows a suppressing effect. (3) There are different threshold effects between capital intensity and technology intensity. The influence of high-tech agglomeration on urban innovation is positive only when the capital intensity exceeds 1.125. However, the influence is always positive in different levels of technology intensity, significantly. When the technology intensity is higher than 9.012E − 06, the degree and significance of this positive impact would decrease. (4) There are heterogeneous impacts of high-tech industry agglomeration on urban innovation output in the Yangtze River Delta urban agglomeration in different time stages, urban innovation development stages, and urban circles.

In this paper, we study the classification problem of large data with many features and strong feature dependencies. This type of problem has shortcomings when handled by machine learning models. Therefore, a classification model with cognitive reasoning ability is proposed. The core idea is to use cognitive reasoning mechanism proposed in this paper to solve the classification problem of large structured data with multiple features and strong correlation between features, and then implements cognitive reasoning for features. The model has three parts. The first part proposes a Feature-to-Image algorithm for converting structured data into image data. The algorithm quantifies the dependencies between features, so as to take into account the impact of individual independent features and correlations between features on the prediction results. The second part designs and implements low-level feature extraction of the quantified features using convolutional neural networks. With the relative symmetry of the capsule network, the third part proposes a cognitive reasoning mechanism to implement high-level feature extraction, feature cognitive reasoning, and classification tasks of the data. At the same time, this paper provides the derivation process and algorithm description of cognitive reasoning mechanism. Experiments show that our model is efficient and outperforms comparable models on the category prediction experiment of ADMET properties of five compounds.This work will provide a new way for cognitive computing of intelligent data analysis.

Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37–0.94, P = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65–0.96, P = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype (P = 0.007 and P = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I–III compared with those with clinical stage IV (P = 0.012 and P = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-A-T haplotype (OR = 0.69, 95% CI = 0.52–0.93, P = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.

The incidence of obesity is increasing worldwide. It was reported that endoplasmic reticulum stress (ERS) could inhibit insulin receptor signaling by activating c-Jun N-terminal kinase (JNK) in the liver. However, the relationship between ERS and insulin receptor signaling in the brain during obesity remains unclear. The aim of the current study was to assess whether ERS alters insulin receptor signaling through the hyper-activation of JNK in the hippocampus and frontal cortex in the brains of obese rats. Obesity was induced using a high fat diet (HFD). The Morris water maze test was then performed to evaluate decreases in cognitive function, and western blot was used to verify whether abnormal insulin receptor signaling was induced by ERS in HFD rats exhibiting cognitive decline. In addition, to determine whether ERS activated JNK and consequently impaired insulin receptor signaling, SH-SY5Y cells were treated with the JNK inhibitor, SP600125, followed by tunicamycin or thapsigargin, and primary rat hippocampal and cortical neurons were transfected with siRNA against IRE1α and JNK. We found that the expression of phosphorylation of PKR-like kinase (PERK), phosphorylation of α subunit of translation initiation factor 2 (eIF2α), and phosphorylation of inositol-requiring kinase-1α (IRE-1α) were increased in the brains of rats with HFD when compared with control rats. The level of serine phosphorylation of insulin receptor substrate-1 (IRS-1) was also increased, while protein kinase B (PKB/Akt) was reduced. ERS was also found to inhibit insulin receptor signaling via the activation of JNK in SH-SY5Y cells, primary rat hippocampal, and cortical neurons. These results indicate that ERS was increased, thereby resulting in impaired insulin receptor signaling in the hippocampus and frontal cortex of obese rats.

Diabetes related cognitive dysfunction (DACD), one of the chronic complications of diabetes, seriously affect the quality of life in patients and increase family burden. Although the initial stage of DACD can lead to metabolic alterations or potential pathological changes, DACD is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of DACD remain somewhat elusive. To understand the pathophysiological changes that underpin the development and progression of DACD, we carried out a global analysis of metabolic alterations in response to DACD. The metabolic alterations associated with DACD were first investigated in humans, using plasma metabonomics based on high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. The related pathway of each metabolite of interest was searched in database online. The network diagrams were established KEGGSOAP software package. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy of metabolites. This is the first report of reliable biomarkers of DACD, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of DACD. The disorders of sphingolipids metabolism, bile acids metabolism, and uric acid metabolism pathway were found in T2DM and DACD. On the other hand, differentially expressed plasma metabolites offer unique metabolic signatures for T2DM and DACD patients. These are potential biomarkers for disease monitoring and personalized medication complementary to the existing clinical modalities.

Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aβ1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aβ1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3β overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD.

Background: The role of artificial intelligence (AI) in the discrimination between pulmonary cryptococcosis (PC) and lung adenocarcinoma (LA) warrants further research. Objectives: To compare the performances of AI models with clinicians in distinguishing PC from LA on chest CT. Methods: Patients diagnosed with confirmed PC or LA were retrospectively recruited from three tertiary hospitals in Guangzhou. A deep learning framework was employed to develop two models: an undelineated supervised training (UST) model utilising original CT images, and a delineated supervised training (DST) model utilising CT images with manual lesion annotations provided by physicians. A subset of 20 cases was randomly selected from the entire dataset and reviewed by clinicians through a network questionnaire. The sensitivity, specificity and accuracy of the models and the clinicians were calculated. Results: A total of 395 PC cases and 249 LA cases were included in the final analysis. The internal validation results for the UST model showed a sensitivity of 85.3%, specificity of 81.0%, accuracy of 83.6% and an area under the curve (AUC) of 0.93. Similarly, the DST model exhibited a sensitivity of 88.2%, specificity of 88.1%, accuracy of 88.2% and an AUC of 0.94. The external validation of the two models yielded AUC values of 0.74 and 0.77, respectively. The average sensitivity, specificity and accuracy of 102 clinicians were determined to be 63.1%, 53.7% and 59.3%, respectively. Conclusions: Both models outperformed the clinicians in distinguishing between PC and LA on chest CT, with the UST model exhibiting comparable performance to the DST model. [ABSTRACT FROM AUTHOR]

Background. The expression of miR-127 has been reported to be decreased in the breast tissue of patients with breast cancer (BRC). However, the mechanism of miR-127 involvement in the pathogenesis of BRC is still unclear and requires urgent clarification. Objectives. To explore the role of miR-127 in the pathogenesis of BRC. Materials and methods. In this study, we measured the expression of miR-127 in blood samples of 60 BRC patients and 60 controls, investigated the influence of miR-127 on the viability and apoptosis of MCF-7 and MDA-231 cells, identified a miR-127 target gene, and determined the expression level of the target gene in the blood samples of BRC patients and controls. Results. We found that miR-127 expression was significantly decreased in the plasma of BRC patients compared to controls. Additionally, the upregulation of miR-127 in MCF-7 and MDA-231 cells inhibited their proliferation and promoted their apoptosis. Conversely, the downregulation of miR-127 promoted cell proliferation and inhibited their apoptosis. The SPP1 was successively predicted and validated as a target gene of miR-127. Finally, the expression level of SPP1 was significantly increased in the plasma of BRC patients compared to controls. Conclusions. Our study demonstrated that decreased miR-127 may promote BRC cell proliferation, inhibit apoptosis and promote the occurrence of BRC through increasing the SPP1 expression level. [ABSTRACT FROM AUTHOR]